How does creatine enhance SSRIs?

Creatine enhances the effects of SSRIs by interacting with the brain's phosphocreatine system, particularly in the forebrain. This interaction appears to be related to the NMDA (N-methyl D-aspartate) receptors, which play a crucial role in neuroplasticity. Neuroplasticity refers to the brain's ability to reorganize itself by forming new neural connections, which is important for mood regulation and response to treatment in depression.

By increasing the activity of the phosphocreatine system, creatine supplementation may improve mood and augment the effects of SSRIs in treating depression. This could result in a lowered required dose of SSRIs or enhanced effectiveness at a given dose, especially noted in women with major depressive disorder. However, the precise mechanisms through which creatine exerts these effects on mood and its relationship with the NMDA receptor are still being investigated 1.